Carcinoembryonic antigen monitoring to detect recurrence of colorectal cancer: how should we interpret the test results?

Shinkins, Bethany, Nicholson, Brian D., James, Timothy J., Primrose, John N. and Mant, David (2014) Carcinoembryonic antigen monitoring to detect recurrence of colorectal cancer: how should we interpret the test results? Clinical Chemistry, 60 (12), 1572-1574. (doi:10.1373/clinchem.2014.228601). (PMID:25161147)

Abstract

To the Editor:

It is routine clinical practice, supported by national guidelines in both North America and Europe, to measure blood carcinoembryonic antigen (CEA)1 to detect recurrence of colorectal cancer during follow-up after primary treatment. Blood CEA is usually measured every 3–6 months, and patients with a CEA concentration above an absolute threshold (5 ?g/L according to American Society of Clinical Oncology guidelines) are investigated further by radiological imaging. However, the evidence underpinning both guidelines and routine practice is weak.

We recently reported the interim results of the Follow-up After Colorectal Surgery (FACS) trial, a clinical trial comparing different types of posttreatment follow-up in 1200 patients with colorectal cancer (1). This trial confirmed that measuring CEA is an effective way of detecting recurrence at an early stage, thus increasing the number of recurrences that can be treated with curative intent. However, the threshold we applied to define an abnormal CEA concentration (7 ?g/L above the patient's postoperative concentration at trial entry) was more conservative than current guidelines, so we decided to reevaluate our data to assess retrospectively whether we could have done better by applying a different strategy to interpret the CEA result and trigger further investigation.

We assessed 3 strategies for interpreting the CEA result based on (a) the result of each test individually; (b) the difference between the individual test result and the patient's own postoperative baseline; and (c) the trend in results over time, calculated by linear regression of the log-transformed CEA values. For each strategy, we assessed the outcome of applying different cutoff thresholds by ROC analysis.

In the CEA arms of the FACS trial, blood CEA was measured every 3 months for 2 years after primary treatment was complete, followed by every 6 months for 3 years. All CEA measurements were made by use of a Siemens Centaur XP analyzer using a chemiluminescence immunoassay, at the John Radcliffe Hospital in Oxford, U.K. (which participates in the national external quality assurance scheme). The analysis we report here is based on 6259 individual CEA measurements in 559 patients (90 of whom experienced recurrence). Patients with <2 CEA measurements, repeat tests, and measurements taken after confirmation of cancer recurrence were excluded.

The ROC curves for each strategy are shown in Fig. 1. This figure illustrates why CEA should not be used as the only method of monitoring, since no strategy achieved 100% diagnostic sensitivity even when applying cutoff thresholds with unacceptably low levels of diagnostic specificity. The figure also shows that calculating the difference from the patient's baseline concentration is no better than considering the result of each test individually [area under the curve (AUC) 0.73 and 0.74]. However, taking account of the trend in CEA concentrations over time was substantially better than either of the other 2 strategies (AUC 0.90, 95% CI 0.85–0.95). The CEA slope that provided maximal diagnostic sensitivity and specificity was a monthly increase of 1.02 ?g/L.

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Contributors

Author: John N. Primrose

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